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Biosci Rep. 2017 Mar 2;37(2). pii: BSR20160574. doi: 10.1042/BSR20160574. Print 2017 Apr 30.

Functional analysis of the mammalian RNA ligase for IRE1 in the unfolded protein response.

Author information

1
Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand.
2
Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, U.S.A.
3
Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand witoon.mu@gmail.com rkaufman@sbpdiscovery.org.
4
Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, U.S.A. witoon.mu@gmail.com rkaufman@sbpdiscovery.org.

Abstract

The unfolded protein response (UPR) is a conserved signalling pathway activated on the accumulation of unfolded proteins within the endoplasmic reticulum (ER), termed ER stress. Upon ER stress, HAC1/XBP1 undergoes exon/intron-specific excision by inositol requiring enzyme 1 (IRE1) to remove an intron and liberate the 5' and 3' exons. In yeast, the 5' and 3' HAC1 exons are subsequently ligated by tRNA ligase (Rlg1p), whereas XBP1 ligation in mammalian cells is catalysed by a recently identified ligase, RtcB. In the present study, RNA ligase activity of the human RtcB (hRtcB) involved in the unconventional splicing of XBP1/HAC1 mRNA was explored in an rlg1-100 mutant yeast strain. Distinct from Escherichia coli RtcB and Rlg1p, expression of hRtcB alone inefficiently complemented HAC1/XBP1 splicing and the hRtcB cofactor (archease) was required to promote enzymatic activity of hRtcB to catalyse RNA ligation.

KEYWORDS:

Rlg1p; archease; human IRE1α/XBP1; human RtcB; rlg1-100

PMID:
28093457
PMCID:
PMC5333776
DOI:
10.1042/BSR20160574
[Indexed for MEDLINE]
Free PMC Article

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